Anti-slit diaphragm antibodies on kidney biopsy identify pediatric patients with steroid-resistant nephrotic syndrome responsive to second-line immunosuppressants

Podocytopathies represent a group of glomerular disorders associated with minimal changes (MC) or focal segmental glomerulosclerosis (FSGS) lesion patterns at biopsy and heterogeneous responses to steroids. Anti-nephrin antibodies were previously found in such patients, suggesting an autoimmune form of podocytopathy. High resolution confocal microscopy on kidney biopsies of a cohort of 128 pediatric patients revealed localization of IgG along the slit diaphragm in 30% of patients with MC and 25% of those with FSGS, but not in other lesion patterns. Anti-nephrin IgG ELISA assay in the serum and stimulated emission depletion microscopy of kidney biopsies showed IgG-nephrin co-localization only in 77.8% of cases. Similar observations were obtained in a cohort of 48 adult patients with MC or FSGS at kidney biopsy, where IgG-nephrin colocalization was only 44.4%, suggesting the existence of autoantibodies binding to other slit proteins. Patients with anti-slit antibodies showed nephrotic syndrome at onset in 94.4% of cases. Patients with primary steroid-resistance had anti-slit antibodies in 27%, while those with secondary steroid-resistance in 87.5% of cases, irrespective of the histopathological lesion pattern. Steroid-resistant patients with anti-slit antibodies responded to second-line immunosuppressants in 92.3% vs. only 20% of patients that were anti-slit negative. No patient with anti-slit antibodies developed kidney failure vs. 51.7% of those negative for antibodies (66.7% with a genetic cause and 41.2% with a non-genetic cause). Thus, the detection of anti-slit antibodies can identify patients with an autoimmune podocytopathy responsive to treatment with second-line immunosuppressants, irrespective of the histopathological lesion pattern at biopsy.

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Publication Details

Journal
Kidney International
Published
2024-10-03
DOI
https://doi.org/10.1016/j.kint.2024.09.006
Citations
53
Primary Topic
Renal Diseases and Glomerulopathies
Type
article
Field-Weighted Citation Impact
17.98

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article

Anti-slit diaphragm antibodies on kidney biopsy identify pediatric patients with steroid-resistant nephrotic syndrome responsive to second-line immunosuppressants

Elisa Buti, Andrea Angeletti, Maria Elena Melica, Letizia De Chiara et al.
53 citations
Kidney International
Renal Diseases and Glomerulopathies
17.98
article

Anti-slit diaphragm antibodies on kidney biopsy identify pediatric patients with steroid-resistant nephrotic syndrome responsive to second-line immunosuppressants

Elisa Buti, Andrea Angeletti, Maria Elena Melica, Letizia De Chiara, Maurizio Bruschi, Benedetta Mazzinghi, Viviana Palazzo, Giulia Antonelli, Gian Marco Ghiggeri, Luigi Cirillo, Paola Romagnani, Josep M. Cruzado, Carolina Conte, Elena Lazzeri, Carmela Errichiello, Samuela Landini, Laura Lasagni, Anna Julie Peired, Francesca Becherucci, Maria Lucia Angelotti, Valentina Raglianti, Marco Allinovi, Fiammetta Ravaglia, Hans‐Joachim Anders, Anna Maria Buccoliero, Anna Montero
article en
53 citations

Abstract

Podocytopathies represent a group of glomerular disorders associated with minimal changes (MC) or focal segmental glomerulosclerosis (FSGS) lesion patterns at biopsy and heterogeneous responses to steroids. Anti-nephrin antibodies were previously found in such patients, suggesting an autoimmune form of podocytopathy. High resolution confocal microscopy on kidney biopsies of a cohort of 128 pediatric patients revealed localization of IgG along the slit diaphragm in 30% of patients with MC and 25% of those with FSGS, but not in other lesion patterns. Anti-nephrin IgG ELISA assay in the serum and stimulated emission depletion microscopy of kidney biopsies showed IgG-nephrin co-localization only in 77.8% of cases. Similar observations were obtained in a cohort of 48 adult patients with MC or FSGS at kidney biopsy, where IgG-nephrin colocalization was only 44.4%, suggesting the existence of autoantibodies binding to other slit proteins. Patients with anti-slit antibodies showed nephrotic syndrome at onset in 94.4% of cases. Patients with primary steroid-resistance had anti-slit antibodies in 27%, while those with secondary steroid-resistance in 87.5% of cases, irrespective of the histopathological lesion pattern. Steroid-resistant patients with anti-slit antibodies responded to second-line immunosuppressants in 92.3% vs. only 20% of patients that were anti-slit negative. No patient with anti-slit antibodies developed kidney failure vs. 51.7% of those negative for antibodies (66.7% with a genetic cause and 41.2% with a non-genetic cause). Thus, the detection of anti-slit antibodies can identify patients with an autoimmune podocytopathy responsive to treatment with second-line immunosuppressants, irrespective of the histopathological lesion pattern at biopsy.

Kidney InternationalVol. 106(6)
Istituto Giannina Gaslini (IT), Bellvitge University Hospital (ES), Meyer Children's Hospital (IT), Azienda Ospedaliero-Universitaria Careggi (IT), Hospital of Prato (IT), University of Florence (IT), Ludwig-Maximilians-Universität München (DE)
Ministero della Salute, Università degli Studi di Firenze, Regione Toscana, Horizon 2020 Framework Programme
Good health and well-being
Openalex Percentile: Top 0%
Renal Diseases and Glomerulopathies
17.98
DOIOpen Access PDFOpenAlex
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